Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome.
Chao Yang, Jason R Siebert, Robert Burns, Zachary J Gerbec, Benedetta Bonacci, Amy Rymaszewski, Mary Rau, Matthew J Riese, Sridhar Rao, Karen-Sue Carlson, John M Routes, James W Verbsky, Monica S Thakar, Subramaniam Malarkannan
Author Information
Chao Yang: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.
Jason R Siebert: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.
Robert Burns: Bioinfomatics Core, Blood Research Institute, Versiti, Milwaukee, WI, USA.
Zachary J Gerbec: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.
Benedetta Bonacci: Flow Cytometry Core, Blood Research Institute, Versiti, Milwaukee, WI, USA.
Amy Rymaszewski: Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. ORCID
Mary Rau: Departments of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
Matthew J Riese: Departments of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA.
Sridhar Rao: Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA. ORCID
Karen-Sue Carlson: Departments of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
John M Routes: Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
James W Verbsky: Departments of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Monica S Thakar: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA.
Subramaniam Malarkannan: Laboratory of Molecular Immunology and Immunotherapy, Blood Research Institute, Versiti, Milwaukee, WI, USA. subra.malar@bcw.edu. ORCID
Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development and heterogeneity of human NK cells are yet to be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct NK populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. Functionally matured NK cells with high expression of CX3CR1, HAVCR2 (TIM-3), and ZEB2 represents terminally differentiated status with the unique transcriptional profile. Transcriptomic and pseudotime analyses identify a transitional population between CD56 and CD56 NK cells. Finally, a donor with GATA2 mutation exhibits reduced percentage of CD56 NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.
